PEP Topic 
Peripheral Neuropathy

Palmitoylethanolamide is a fatty acid compound that may inhibit the release of pro-inflammatory mediating compounds from mast cells. This endogenous substance has been associated with effects on neuroinflammation and reduction in neuropathic pain syndromes in some clinical conditions. Palmitoylethanolamide was studied for its effect on chemotherapy-induced peripheral neuropathy.

Effectiveness Not Established

Research Evidence Summaries

Truini, A., Biasiotta, A., Di Stefano, G., La Cesa, S., Leone, C., Cartoni, C., . . . Cruccu, G. (2011). Palmitoylethanolamide restores myelinated-fibre function in patients with chemotherapy-induced painful neuropathy. CNS & Neurological Disorders - Drug Targets, 10, 916-920.

DOI: 10.2174/187152711799219307

Study Purpose:

Assess the effect of palmitoylethanolamide (PEA) on pain and nerve function in patients with chemotherapy-induced painful neuropathy receiving bortezomib and thalidomide for multiple myeloma.

Intervention Characteristics/Basic Study Process:

Patients with a score of at least 4 on a Douleur Neuropathique 4 (DN4) screening tool for neuropathic pain were given 600 mg daily for two months during treatment with bortezomib and thalidomide. Study measurements were done before and after the administration of palmitoylethanolamide (PEA).

Sample Characteristics:

  • N = 20   
  • AGE = Not stated
  • MALES and FEMALES (%) = Not stated
  • KEY DISEASE CHARACTERISTICS: All patients had multiple myeloma.
  • OTHER KEY SAMPLE CHARACTERISTICS: All patients had touch/vibration hypoesthesia, seven had hyoalfesia, and five had abnormal thermal sensation. All had ongoing pain. None had paroxysmal pain or allodynia.


  • SITE: Single site
  • SETTING TYPE: Outpatient
  • LOCATION: Italy

Phase of Care and Clinical Applications:

PHASE OF CARE: Active antitumor treatment

Study Design:

Prospective trial

Measurement Instruments/Methods:

  • Nerve assessment for touch, vibration, and pinprick sensation
  • Warmth sensation threshold assessed with yttrium aluminum perovskite (YAP) laser
  • Motor and sensory nerve conduction studies


In four patients, the chemotherapy dose was reduced due to non-neuropathic problems. After two months of treatment with PEA, pain scores were significantly reduced (p < .002). Warmth threshold was not significantly changed. Ulnar, sural, and peroneal amplitudes were significantly increased (p < .03).


PEA may be of benefit in reducing pain and improving myelinated fibre function in patients who have chemotherapy-induced neuropathic symptoms.


  • Small sample of < 30
  • Risk of bias (no control group) 
  • Risk of bias (no blinding)
  • Risk of bias (no random assignment)
  • Measurement/methods were not well described.
  • Method of pain measurement was not described.
  • Patient demographic characteristics were not described.

Nursing Implications:

PEA may be a therapeutic tool for patients with painful chemotherapy-induced peripheral neuropathy; however, significant limitations as seen in this study contribute to a lack of evidence strength in this area. Further research of this intervention is warranted, as there are few known effective interventions for this problem.